Gadolinium Deposition Disease Risk from MRI Contrast Agent

Magnetic resonance imaging (MRI) has become a standard diagnostic tool. Radiologists who administer an MRI sometimes use gadolinium-based contrast agents (GBCAs) to improve the quality of the image. Many members of the international medical community agree that some GBCAs can have long-term effects on the body and brain. The risk that patients will develop gadolinium deposition disease (GDD) is one of the most serious potential consequences of using GBCAs to perform an MRI.

Gadolinium is a heavy metal. Like other heavy metals, including arsenic and mercury, it can be toxic, even at low levels. Gadolinium blocks the movement of calcium into certain muscle cells and harms bodily functions that depend upon an influx of calcium ions.

Introducing gadolinium alone into the human body could expose patients to serious health risks. To minimize the risk of harm, doctors use a GBCA that is designed to shield the body from gadolinium by chemically binding it to chemical compounds known as chelating agents.

Why Are GBCAs Used in MRIs?

Doctors use X-rays to detect broken bones, but an X-ray does not provide a detailed view of the body’s tissues and organs. An MRI, like a PET scan and an ultrasound, allows physicians to get a better look at tissues and organs inside a patient’s body.

An MRI scanner creates a magnetic field that causes the hydrogen atoms inside the body to line up in the direction of the field. Most hydrogen atoms line up in pairs, but some do not. Directing a radio frequency pulse into the magnetic field causes the unpaired hydrogen atoms to absorb energy and reverse the direction of their spin. When the pulse is turned off, the unpaired atoms release that energy. The MRI scanner detects the speed with which the energy is released. Computer software converts that data into an image that represents a narrow slice of the body’s tissues. A series of MRI images provide a map of tissues within the part of the body that was subjected to the MRI field.

Doctors sometimes inject a GBCA into a patient to improve the quality of MRI images. Gadolinium is attracted by magnetism, and its presence in the body alters the magnetic properties of hydrogen atoms. A GBCA affects the rate of the atom’s return to its original state, creating a stronger signal for the software to interpret. Using a GBCA therefore creates images with finer definition and enhanced clarity.

Not every MRI scan uses a GBCA. Radiologists are most likely to use a GBCA when they want to improve the visibility of tumors, blood vessels, inflammation, scarring of heart muscles, and certain bodily tissues. A GBCA is used in about 30% of all MRI scans.

While doctors believed for many years that GBCAs were safe and effective, concerns about gadolinium retention in the body began to surface in the 1990s. Initial concerns focused on the use of GBCAs when scanning patients for kidney disease. Certain kidney injuries after an MRI were thought to be related to large doses of a GBCA. Radiologists responded by adjusting GBCA dosages for patients with kidney diseases.

In the late 1990s, doctors identified a disease known as nephrogenic systemic fibrosis (NSF), a rare and incurable disorder that affects skin, joints, and internal organs. The disorder only affects patients with kidney disease. A 2006 study identified GBCAs used in MRIs as a cause of the disorder. In 2010, the Food and Drug Administration (FDA) required warnings to be added to GBCA labels to minimize the risk that patients with kidney diseases would receive GBCA dosages that would lead to NSF.

New concerns began to arise in 2013 when Japanese researchers found evidence that gadolinium accumulates in the brain when GBCAs are used in MRI scans. Scientists discovered that successive MRIs using a GBCA increased the amount of gadolinium that is deposited in the brain. A 2015 study by physicians at Mayo Clinic confirmed the existence of gadolinium deposits in the brains of patients who had undergone at least four brain scans using a GBCA.

Researchers suspect that deposits occur when gadolinium ions escape from the chelating ligand molecules to which they are bound in GBCAs. Chelating ligands can be either linear (chained) or macrocyclic (ring structured). Studies in rats suggest that macrocyclic ligands are more likely to prevent the escape of gadolinium than linear molecules. A GBCA with a linear structure may therefore be less safe than a GBCA with a macrocyclic structure.

In addition, researchers compared linear nonionic GBCA to linear ionic GBCA. That study found deposits of gadolinium in the brains of patients who had MRI scans using linear nonionic GBCA but not in the brains of patients who had MRI scans using linear ionic GBCA.

The best current research therefore suggests that the safest GBCAs are both macrocyclic and ionic while the least safe GBCAs are both linear and nonionic. GBCAs that are both linear and ionic or macrocyclic and nonionic appear to fall in the middle of the safety continuum.

The two widely marketed linear nonionic GBCAs are sold under the brand names Omniscan and OptiMARK. GE Healthcare markets Omniscan while OptiMARK is marketed by Mallinckrodt Pharmaceuticals. In 2010, the European Agency for the Evaluation of Medicinal Products described Omniscan and OptiMARK, as well as Magnevist (a linear ionic agent manufactured by Bayer) as “high risk” agents for patients who were susceptible to NSF.

The European Medicines Agency, a regulatory agency that is similar to the Food and Drug Administration (FDA), recently restricted or banned the use or marketing of many linear GBCAs in Europe. Regulators in Japan have also restricted the use of GBCAs. The FDA is traditionally slow to limit the use of drugs it has previously approved, but it recently acknowledged that linear GBCAs “result in more retention and retention for a longer time than macrocyclic GBCAs” and that gadolinium levels remaining in the body “are higher after administration of Omniscan (gadodiamide) or OptiMARK (gadoversetamide).” The FDA now requires patients to be given a Medication Guide so they can make an informed choice about whether to have an MRI using a GBCA.

What Are the Consequences of Gadolinium Deposits in the Brain?

A number of radiologists expressed concerns about the potential toxic effects of gadolinium buildup in the brain at the 2017 Radiological Society of North America (RSNA) meeting last November. Some radiologists fear liability for exposing patients to GBCAs and are therefore reluctant to acknowledge that deposits of a heavy metal in a patient’s brain might have adverse effects. Patient advocacy groups, however, cite a growing body of evidence that GBCAs are responsible for gadolinium deposition disease.

Some patients may be more genetically susceptible to GDD than others. Unlike NSF, however, patients who have acquired GDD are not limited to those who have a preexisting kidney disease. Since it is difficult to predict whether a particular patient is vulnerable to GDD, all patients should be aware of the risk so that they can make an informed choice about whether, and how often, to have an MRI using a GBCA.

A patient who undergoes an MRI that does not use a GBCA has no reason to worry about GDD. When a radiologist decides to use a GBCA, existing evidence suggests that the risk of acquiring GDD is greatest when the radiologist uses a linear nonionic GBCA, such as OMNISCAN or OptiMARK. While other GBCAs might also cause GDD, they carry less risk. It is fair to say that the greatest risk is associated with repeated exposures to linear nonionic GBCAs and that the least risk is associated with macrocyclic ionic GBCAs.

Quantifying the risk is difficult. Since deposits of gadolinium in the brain seem to be cumulative, however, the evidence suggests that the more often a patient undergoes an MRI using a GBCA, the more likely it is that the patient will acquire GDD.

To minimize the risk to patients undergoing an MRI, the National Institutes of Health recommend that radiologists refrain from using a GBCA unless there is a clear need to do so. The NIH also recommends that radiologists use a macrocyclic GBCA unless patients have an allergy that requires the use of a linear GBCA. Avoiding repeated MRIs using a GBCA is also a wise precaution.

How Do I Know if I Am at Risk of Developing GDD?

If you were injected with a substance in anticipation of having an MRI, you were probably given a GBCA. You can contact the medical records department of the clinic or hospital where it was performed to find out what kind of GBCA was administered.

A urine test can determine whether you have gadolinium in your system. If you have any of the symptoms described above and you were given a GBCA, you might have GDD. A lawyer at Advocate Law Group can advise you about the steps you can take to protect your rights.

Advocate Law Group represents patients with GDD in claims against the manufacturers and distributors of GBCAs. You may be entitled to compensation if you have GDD, but you should contact Advocate Law Group promptly to avoid losing your right to seek a legal remedy for your condition.

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